Prostate-Specific Antigen Response at Six Months Predicts Progression in Metastatic Hormone-Sensitive Prostate Cancer Treated With Apalutamide.

Background: PSA response to apalutamide combined with androgen deprivation therapy (ADT) in metastatic hormone-sensitive prostate cancer (mHSPC) has been linked to prognosis. Post hoc analyses from clinical trials suggest that PSA levels at 6 months are critical for predicting radiographic progression-free survival (rPFS) and overall survival (OS). Real-world evidence (RWE) is needed to confirm these findings.

Materials and methods: This multicentre, retrospective study included patients with mHSPC treated with apalutamide plus ADT from May 2018 to January 2025 across 18 Spanish centers. Patients were stratified according to PSA level at 6 months: Complete response (CR; ≤ 0.2 ng/mL) or incomplete response (IR; > 0.2 ng/mL). The primary objective was to evaluate the association between PSA response and rPFS at 24 and 36 months. Univariate and multivariate Cox regression analyses were used to identify predictors of progression.

Results: Among 812 patients, 65% achieved a CR at 6 months, associated with higher rPFS at 24 (94%) and 36 (81%) months compared to the IR group (73% and 60%, respectively; p < 0.0001). CR (hazard ratio: 0.38; p < 0.001) and low-volume disease (hazard ratio: 0.41; p < 0.001) were independent predictors of rPFS. Baseline PSA, disease volume, and positron emission tomography imaging predicted achieving a CR.

Conclusions: In this large real-world cohort, PSA response at 6 months was a strong predictor of disease progression, supporting its use as a dynamic prognostic biomarker.